Recurrent ulcers of the oral cavity at some period during life are exceedingly common in the general population (20-50%). This proposal examines the role of circulating immune complex-mediated (CIC) vessel damage and polymorphonuclear leukocyte (PMNL) function in the pathogenesis of recurrent aphthous ulceration. Two disease models, Behcet's syndrome (BS-10 patients) and complex aphthosis (the occurrence of recurrent oral and genital aphthae or almost constant, multiple oral aphthae-CA-10 patients) are employed in this proposal. CIC will be evaluated by two in vitro assays, Raji cell and Clq binding, and by the in vivo Braverman's histamine trap test. The in vivo test involves immunohistopathologic (4 hours) and routine histopathologic (24 hours) evaluation of intradermal histamine-induced pathergy lesions for immunoreactant deposition in dermal blood vessels and for leukocytoclastic (CIC-mediated) vasculitis respectively. In addition, patient and control serum effects on PMNL migration will be assessed using both subagarose and Boyden chamber methodology. An important hypothesis to be tested in this proposal is that mucocutaneous lesions in patients with BS and CA are in part produced by inappropriate PMNL migration. The adhesive glycoprotein complex (LFA-1/Mac-1/pl50,95) was recently established as a major determinant and regulator of PMNL movement. The expression of the adherence glycoprotein complex on the PMNL surface of patients will be determined by fluorescence activated flow cytometry utilizing monoclonal antibodies against the alpha subunits of LFA-1, Mac-1, pl50,95, and the common beta subunit. In addition, the quantitation of intracellular pools of the adhesive glycoprotein complex will be assessed after disruption of the cells by nitrogen cavitation and subsequent fractionation of Percoll gradients. Quantitation of subcellular amounts of the adhesive glycoproteins will be accomplished by radioimmunoassay. Clinical therapy with either oral thalidomide or oral colchicine will be evaluated in appropriate patient groups using a single blind serial design in which each patient serves as their own control. This mechanism oriented assessment of thalidomide and colchicine therapy will address the relative contribution of PMNL and CIC effects in these two disease models (BS and CA). Information gained in this study will be important for understanding host defense factors in other oral diseases such as juvenile and adult periodontitis.